Lower socioeconomic status is associated with delayed access to care for infantile hemangioma: A cohort study.

BACKGROUND: Early specialist evaluation during rapid proliferative growth of complicated infantile hemangiomas (IHs) is crucial. Health disparities and barriers of access to care for children with IHs have not been examined. OBJECTIVE: To investigate whether socioeconomic status (SES) is associated with age at presentation to a subspecialist for IH evaluation. METHOD: A retrospective cohort study of 804 children presenting to a large academic hospital. The primary outcome was age at initial presentation. Covariates included demographic, socioeconomic, geographic, and clinical characteristics. Medicaid and the Children's Health Insurance Program were proxies for lower SES. Analysis of covariance, chi-square tests, and generalized ordered logistic regressions were performed. RESULTS: Children with lower SES had higher odds of presenting after 3 months of age (odds ratio, 2.11; 95% confidence interval, 1.31-3.38). In the subset that qualified for the institutional care management program (ICMP), no risk factors were associated with delayed presentation. LIMITATIONS: Use of insurance and economic distress as proxies for SES; exclusion of uninsured children, which may have resulted in underestimation of racioethnic effects; and examination of a single academic center, which may limit generalizability. CONCLUSIONS: Children with IHs and lower SES were more likely to present later to specialists, but those enrolled in an ICMP were not, suggesting that integrated ICMPs may mitigate disparities and delayed access to care for IHs among lower-SES populations.

Limited utility of repeated vital sign monitoring during initiation of oral propranolol for complicated infantile hemangioma.

BACKGROUND: Initial propranolol recommendations for infantile hemangioma published in 2013 were intended as provisional best practices to be updated as evidence-based data emerged. METHODS: A retrospective multicenter study was performed to evaluate utility of prolonged monitoring after first propranolol dose and escalation(s). Inclusion criteria included diagnosis of hemangioma requiring propranolol of greater than or equal to 0.3 mg/kg per dose, younger than 2 years, and heart rate monitoring for greater than or equal to 1 hour. Data collected included demographics, dose, vital signs, and adverse events. RESULTS: A total of 783 subjects met inclusion criteria; median age at initiation was 112 days. None of the 1148 episodes of prolonged monitoring warranted immediate intervention or drug discontinuation. No symptomatic bradycardia or hypotension occurred during monitoring. Mean heart rate change from baseline to 1 hour was -8.19/min (±15.54/min) and baseline to 2 hours was -9.24/min (±15.84/min). Three preterm subjects had dose adjustments because of prescriber concerns about asymptomatic vital sign changes. No significant difference existed in pretreatment heart rate or in heart rate change between individuals with later adverse events during treatment and those without. CONCLUSION: Prolonged monitoring for initiation and escalation of oral propranolol rarely changed management and did not predict future adverse events. Few serious adverse events occurred during therapy; none were cardiovascular.

Management of infantile hemangiomas during the COVID pandemic.

The COVID-19 pandemic has caused significant shifts in patient care including a steep decline in ambulatory visits and a marked increase in the use of telemedicine. Infantile hemangiomas (IH) can require urgent evaluation and risk stratification to determine which infants need treatment and which can be managed with continued observation. For those requiring treatment, prompt initiation decreases morbidity and improves long-term outcomes. The Hemangioma Investigator Group has created consensus recommendations for management of IH via telemedicine. FDA/EMA-approved monitoring guidelines, clinical practice guidelines, and relevant, up-to-date publications regarding initiation and monitoring of beta-blocker therapy were used to inform the recommendations. Clinical decision-making guidelines about when telehealth is an appropriate alternative to in-office visits, including medication initiation, dosage changes, and ongoing evaluation, are included. The importance of communication with caregivers in the context of telemedicine is discussed, and online resources for both hemangioma education and propranolol therapy are provided.

Evaluating the Safety of Oral Propranolol Therapy in Patients With PHACE Syndrome.

Importance: Oral propranolol is widely considered to be first-line therapy for complicated infantile hemangioma, but its use in patients with PHACE (posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects, eye anomalies) syndrome has been debated owing to concerns that the cardiovascular effects of the drug may increase the risk for arterial ischemic stroke. Objective: To assess the incidence of adverse events among patients with PHACE syndrome receiving oral propranolol for infantile hemangioma. Design, Setting, and Participants: This multicenter retrospective cohort study assessed the incidence of adverse events among 76 patients with PHACE syndrome receiving oral propranolol for infantile hemangioma at 11 tertiary care, academic pediatric dermatology practices. Medical records from January 1, 2010, through April 25, 2017, were reviewed. Exposures: Patients received oral propranolol, 0.3 mg/kg/dose or more. Main Outcomes and Measures: The main outcome was the rate and severity of adverse events occurring throughout the course of treatment with oral propranolol, as documented in the medical records. Adverse events were graded from 1 to 5 using a scale derived from the Common Terminology Criteria for Adverse Events and were considered to be serious if they were grade 3 or higher. Results: A total of 76 patients (59 girls and 17 boys; median age at propranolol initiation, 56 days [range, 0-396 days]) met the inclusion criteria. There were no reports of serious adverse events (ie, stroke, transient ischemic attack, or cardiovascular events) during treatment with oral propranolol. A total of 46 nonserious adverse events were reported among 29 patients (38.2%); the most commonly reported nonserious adverse events were sleep disturbances and minor gastrointestinal tract and respiratory tract symptoms. In a comparison with 726 infants who received oral propranolol for hemangioma but did not meet criteria for PHACE syndrome, there was no significant difference in the rate of serious adverse events experienced during treatment (0 of 76 patients with PHACE syndrome and 3 of 726 patients without PHACE syndrome [0.4%]). Conclusions and Relevance: This study found that oral propranolol was used to treat infantile hemangioma in 76 patients with PHACE syndrome and that no serious adverse events were experienced. These data provide support for the safety of oral propranolol in this patient population.

Periocular infantile hemangiomas: Characteristics, ocular sequelae, and outcomes.

OBJECTIVES: To identify clinical factors associated with complications of periocular infantile hemangioma (IH) and monitor improvement in complication rates post-treatment. METHODS: Retrospective cohort study. Eighty-nine patients diagnosed with periocular IH at a pediatric dermatology clinic of a tertiary care center between 2001 and 2013 were included with parental approval. Parents were interviewed by telephone between July and September of 2015, then again in January 2018 to inquire about ophthalmologic follow-up. Electronic medical records were reviewed from January 2001 through January 2018. RESULTS: Sixty percent of patients demonstrated ocular sequelae, including astigmatism (33%), visual axis obstruction (29%), nasolacrimal duct obstruction (7%), ptosis (4%), amblyopia (3%), and strabismus (1%). Compared with superficial IH, deep and mixed IH had higher odds, 3.4 (P = 0.025) and 3.8 (P = 0.034), respectively, of developing ocular sequelae. All patients with astigmatism prior to involution of IH received systemic therapy, with a significant post-treatment decrease in the proportion of patients with astigmatism (40% to 18%, P = 0.027). Three-quarters of patients experienced complete IH involution by time of enrollment in kindergarten. Fifty-one (57.3%) patients received formal ophthalmologic evaluation confirmed through chart review or phone interview, with average follow-up duration of 51.2 months (range: 1.9, 99.3). CONCLUSION: Deep and mixed IH were more likely to demonstrate ocular complications than superficial IH. Rate of astigmatism decreased with systemic therapy. Our study suggests that patients with periocular IH have a lower rate of amblyopia now compared with the prepropranolol era and emphasizes the importance of early treatment of periocular IH to prevent permanent visual sequelae.

Fractional CO2 Laser Treatment Outcomes for Pediatric Hypertrophic Burn Scars.

Carbon dioxide ablative fractional laser (CO2-AFL) therapy has not been widely adopted in pediatric burn care given limited outcomes literature and no established guidelines on laser treatment protocols. We present our experience to further elucidate the clinical role of CO2-AFL therapy for pediatric hypertrophic burn scars. We conducted a prospective cohort study of pediatric burn patients undergoing CO2-AFL treatment of hypertrophic, symptomatic burn scars at a tertiary care regional burn center during a 2-year period. Scars were assessed before each treatment using the Patient and Observer Scar Assessment Scale (POSAS), a validated, subjective, comprehensive scar assessment tool. We treated 49 pediatric patients for a total of 180 laser sessions. Burn severity was full thickness (63.6%) or deep partial thickness (47.7%). Observer-rated POSAS scores revealed statistically significant improvements in pigment, thickness, relief, pliability, and surface area after one treatment with continued improvement until the last laser session. Patient-rated POSAS revealed statistically significant improvements in color, stiffness, thickness, and irregularity after laser treatments. Total POSAS improved from 89.6 ± 17.5 to 76.6 ± 16.8 (P < .0001) after one treatment with further improvement to 69.2 ± 14.9 (P < .0001) at the final laser session. We found convincing evidence that CO2-AFL therapy improves hypertrophic burn scars on both patient- and observer-rated scales confirming statistical and clinical significance to both providers and families. These findings demonstrate that CO2-AFL can improve hypertrophic burn scars in pediatric patients providing a lower risk alternative to invasive therapies and a more immediate, efficacious alternative to more conservative scar treatments.

Topical timolol as adjunct therapy to shorten oral propranolol therapy for infantile hemangiomas.

BACKGROUND/OBJECTIVES: First-line therapy for infantile hemangiomas (IH) is oral propranolol, a systemic beta-blocker with the risk of rare but serious adverse effects. Topical timolol presents an attractive off-label alternative with good tolerability, but sequential therapy with propranolol followed by timolol is not well studied. Here, we report effects of topical timolol preceding or following oral propranolol as adjunct therapy for IH. METHODS: A retrospective chart review of 559 patients with IH seen at the pediatric dermatology clinic of a tertiary care center between December 2008 and January 2018. Children were grouped by treatment received: propranolol only, timolol only, propranolol to timolol, timolol to propranolol to timolol, and timolol to propranolol. Patient demographics, clinical/treatment characteristics, and pairwise differences were explored between groups. RESULTS: Among all patients treated with propranolol, those who received propranolol followed by timolol received the shortest duration of oral propranolol and were the youngest at the time of propranolol completion. These patients received propranolol for a median of 2.2 months duration (P = 0.006) and were a median of 1.7 months younger (P = 0.007) compared with patients who received oral propranolol only. None had treatment failure defined as requiring propranolol reinitiation, compared with 13% of patients in the propranolol only group (P = 0.036). CONCLUSIONS: Sequential therapy with oral propranolol followed by topical timolol for IH may help minimize potential adverse effects of systemic beta-blockers by reducing the duration of propranolol therapy and facilitating successful taper at a younger age without an increase in treatment failures.

Bilateral Eccrine Angiomatous Hamartoma with Symmetric Volar Wrist Nodules: A Case Report.

CASE: We describe a 13-year-old girl with bilateral symmetric eccrine angiomatous hamartoma (EAH) on the volar aspect of the wrists. The lesions were painless and had been enlarging progressively for 1 year; the enlargement of the nodule on the right wrist was more substantial than that on the left wrist. She had palmar hyperhidrosis, which has a known association with EAH. CONCLUSION: To our knowledge, bilateral symmetric EAH has been reported only 3 other times in the literature. In all 3 of these cases, the lesions were on the dorsum of the hands or the wrists. We believe that this is the first report of this rare presentation on the volar aspect of the wrist. The symmetry suggests that the lesions may be the manifestation of a systemic or mechanical cause.

An Interdisciplinary Approach to Treatment of Adult Facial Arteriovenous Malformations: A Review of the Literature and A Single Institution's Experience With "Late" Surgical Resection and Aesthetic Reconstruction.

BACKGROUND: Arteriovenous malformations (AVMs) are high flow vascular anomalies that are difficult to manage given their high recurrence rate. At this time, the optimal treatment of AVMs involves embolization and surgical resection. However, few studies have examined patient outcomes after a delayed surgical resection approach. METHODS: A retrospective chart review of all patients presenting to a single institution with vascular malformations from 2000 to 2016 was performed. Patients with facial AVMs that underwent operative management were included. Records were reviewed for patient characteristics, lesion natural history, operative timing after embolization (<72 vs >72 hours), and outcomes. RESULTS: 11 patients fulfilled the inclusion/exclusion criteria. Nine patients were female, with an average age at resection of 29.1 years. Three patients had hemi/mid-facial AVMs, 1 patient had a nasal AVM, 3 patients had labial AVMs, 1 patient had an AVM on the chin, and 1 had a periorbital AVM. Average time between embolization and primary resection was 8.6 days (range 1-24). No complications requiring reoperation occurred in any patient. Average follow-up was 32.6 months, with 2 recurrences at a mean of 47.6 months. Timing of resection, Schobinger stage, and resection completeness did not significantly affect recurrence (P >0.05). Lesion size >6 cm in any dimension was significantly associated with recurrence (P = 0.018). CONCLUSION: Compared to early resection, delayed (>72 h) surgical resection after embolization of facial AVMs is a viable treatment option and results in non-inferior recurrence rates (25 vs 14% respectively over a 40-month period).

Itching at night: A review on reducing nocturnal pruritus in children.

The most common causes of chronic nocturnal itching in children are atopic dermatitis and psoriasis, with lichen simplex chronicus and prurigo nodularis contributing to lesser degrees. Despite the prevalence of nocturnal itching, its pathophysiology remains poorly understood. The most troubling consequence of itching at night is poor quality of sleep. Poor sleep quality in children with nocturnal itching has been linked to adverse neurocognitive, behavioral, and physiologic outcomes, including poor performance in school, attention deficit hyperactivity disorder, short stature, hypertension, obesity, and impaired immune function. There is no consensus on the best management of nocturnal itching in children. We conducted a review of the literature evaluating the efficacy of various treatment options for children with chronic nocturnal pruritus. Our review found three recently conducted randomized controlled trials and one case report demonstrating the efficacy of topical corticosteroids, oral melatonin, and clonidine in reducing nocturnal itching or improving sleep quality in children with nocturnal pruritus. Future research is needed to elucidate the pathophysiology of nocturnal itching to best develop targeted, effective treatment strategies.

Scarring in Patients With PIK3CA-Related Overgrowth Syndromes.

Importance: Patients with somatic overgrowth commonly require surgical intervention to preserve function and improve cosmesis. To our knowledge no observation of scarring outcomes in this population has been published to date. Objective: To observe the frequency of abnormal scarring in patients with somatic overgrowth and sequencing-verified mutations in the PIK3CA gene. Design, Setting, and Participants: This retrospective study evaluated scarring outcomes in patients with PIK3CA-related overgrowth. Samples of affected tissue were sequenced between July 2015 and October 2016. Medical records from multiple large academic tertiary care centers were reviewed for surgical history and scar descriptions, and clinical photographs were assessed by 2 surgeons (J.N.J. and D.M.K.) to confirm abnormal scarring. Analysis of medical records and photographs was performed between April 2017 and June 2017 by a multidisciplinary team from dermatology, plastic surgery, orthopedic surgery, radiology, and genetics departments. All patients considered for the study were diagnosed with somatic overgrowth and previously had affected tissue sent for next-generation sequencing. Those with pathogenic PIK3CA variants and 1 or more prior surgical procedures were reviewed. Main Outcomes and Measures: Presence of excessive scarring in patients with PIK3CA overgrowth. Results: A total of 57 patients with segmental overgrowth syndromes were sequenced. Of the 57 patients, 25 (44%) had pathogenic or likely pathogenic variants in PIK3CA. Of those with pathogenic PIK3CA variants, 6 (24%) had past surgical procedures, all with preoperative and postoperative photographs. Of 6 patients with PIK3CA-related overgrowth and a history of 1 or more surgical procedure, 4 (67%) developed excessive scarring. The cohort with abnormal scarring comprised 3 females and 1 male, with a median age of 8.5 years. All abnormal scarring occurred in affected overgrowth tissue. Three of the 4 patients developed the excessive scarring after debulking procedures for overgrowth and/or vascular malformations of the upper or lower extremity. Conclusions and Relevance: Excessive scarring occurred frequently in patients with PIK3CA-related overgrowth syndromes. The risk of abnormal scarring should therefore be discussed preoperatively. Given the activating nature of these PIK3CA variants, we suggest that the excessive scarring may be owing in part to up-regulation of the PI3K-Akt-mTOR pathway. Additional studies are needed to assess scarring outcomes in patients with other types of overgrowth.

Demographic characteristics of teenage boys with horizontal striae distensae of the lower back.

BACKGROUND: This study examines the clinical characteristics and demographics of teenage boys with horizontal striae distensae of the lower back in an outpatient setting. METHODS: Retrospective medical chart reviews and telephone survey studies were completed on an outpatient cohort of 12 boys 11 to 17 years of age with a clinical diagnosis of transverse striae distensae of the lower back at a single-center, university-based, pediatric dermatology practice. We evaluated the clinical features of the striae, participant demographic characteristics, and past medical history. A review of the literature concerning risk factors was conducted using PubMed and Google Scholar. RESULTS: Of the 14 patients we contacted, 12 agreed to participate. The average age of onset for the striae was 14.3 years. All boys were above the 50th percentile in height at the time of onset. Eight (66.7%) reported a significant growth spurt before the appearance of the stretch marks. Most were asymptomatic. None of the boys had a history of unmonitored exogenous steroid use or prior infection with Bartonella henselae or Borrelia burgdorferi. Only one (8.3%) had a chronic medical condition. Eleven (91.7%) had at least one first-degree relative with striae distensae. CONCLUSION: Our results indicate that horizontal striae distensae of the lower back in adolescent boys is associated with a rapid growth spurt, tall stature, and family history of striae distensae. There is no association between this type of striae distensae and any chronic medical condition, bacterial infection, or exogenous steroid use. Thus a careful review of systems and counseling without further medical testing is reasonable management.

Retrospective Study of Nasal Infantile Hemangiomas: Characteristics, Complications, and Outcomes.

BACKGROUND/OBJECTIVES: Nasal infantile hemangiomas (IHs) pose serious medical complications and psychosocial stress if tumor involution is incomplete or prolonged. The objective was to determine which IH characteristics are associated with complications and are predictive of outcome, assessed as the presence of IHs or residual skin changes upon kindergarten entry, to better manage these lesions and counsel families. METHODS: A retrospective chart review of all patients seen in the Division of Pediatric Dermatology at Johns Hopkins Medicine between 2001 and 2014 for nasal IHs (N = 89) was performed. A follow-up telephone interview with parents was conducted in June and July 2014. RESULTS: Complications were observed in 39% of patients. Segmental and indeterminate IHs were more likely to have complications than focal IHs (p = 0.01). Mixed IHs were more likely to ulcerate than deep or superficial IHs (p = 0.01). Eighty percent of patients had treatment and 19% had surgery. Although IHs regressed by kindergarten entry in 70% of patients, 78% of these patients had residual skin changes. Mixed and superficial IHs left more residua than deep IHs (p = 0.04). A statistical comparison of treatments with respect to outcome at kindergarten entry could not be made because subgroups were too small and heterogeneous. CONCLUSION: Nasal IHs had higher rates of complications and treatment than previous reports of IHs at all body sites. Lesions of segmental and indeterminate type and mixed depth should be identified as high risk and treated accordingly. Parents may be counseled that most nasal IHs involute by kindergarten but leave residua and that early referral for treatment may be important for the best outcome.

Genetic basis for vascular anomalies.

The fundamental genetics of many isolated vascular anomalies and syndromes associated with vascular anomalies have been elucidated. The rate of discovery continues to increase, expanding our understanding of the underlying interconnected molecular pathways. This review summarizes genetic and clinical information on the following diagnoses: capillary malformation, venous malformation, lymphatic malformation, arteriovenous malformation, PIK3CA-related overgrowth spectrum (PROS), Proteus syndrome, SOLAMEN syndrome, Sturge-Weber syndrome, phakomatosis pigmentovascularis, congenital hemangioma, verrucous venous malformation, cutaneomucosal venous malformation, blue rubber bleb nevus syndrome, capillary malformation-arteriovenous malformation syndrome, Parkes-Weber syndrome, and Maffucci syndrome.

Topical Timolol Maleate Treatment of Infantile Hemangiomas.

BACKGROUND: There has been a dramatic increase in the off-label use of ophthalmic timolol maleate, a ß-blocker used for infantile hemangioma (IH) treatment as a topical counterpart to oral propranolol. Its safety and efficacy in a pediatric population with IH have not been evaluated in a large cohort. Our goal was to retrospectively assess timolol's effectiveness, discern characteristics associated with response, and document reported adverse events. METHODS: A multicenter retrospective cohort study of 731 patients treated with topical timolol was completed at 9 centers. Inclusion required an IH suitable for timolol in the treating physician's judgment and access to clinical details including photographs. Logistic regression analysis and descriptive statistics were performed. Primary outcome measures were efficacy assessed by using visual analog scales for color and for size, extent, and volume from review of digital photographs taken as standard of care. RESULTS: Most IHs were localized (80.1%) and superficial (55.3%). Risk of disfigurement was the most common indication for therapy (74.3%). Duration of therapy (P < .0001), initial thinness (P = .008), and subtype (P = .031) were significant predictors of response. Best response occurred in superficial IHs <1 mm thick. Fifty-three (7.3%) required subsequent therapy with systemic ß-blocker. Adverse events were mild, occurring in 25 (3.4%) patients. No cardiovascular side effects were documented. CONCLUSIONS: Timolol seems to be a well-tolerated, safe treatment option with moderate to good effectiveness, demonstrating best response in thin, superficial IHs regardless of pretreatment size. Timolol can be recommended as an alternative to systemic ß-blockers and watchful waiting for many patients.

Diagnosis and management of infantile hemangiomas.

Propranolol has replaced corticosteroids as preferred first-line therapy for the management of infantile hemangiomas (IH). The topical ß-blocker timolol is now an alternative to oral propranolol and watchful waiting for smaller IH. Research in the last decade has provided evidence-based data about natural history, epidemiology, and syndromes associated with IH. The most pressing issue for the clinician treating children with IH is to understand current data to develop an individualized risk stratification for each patient and determine the likelihood of complications and need for treatment. This article emphasizes the nuances of complicated clinical presentations and current treatment recommendations.

Propranolol vs prednisolone for symptomatic proliferating infantile hemangiomas: a randomized clinical trial.

IMPORTANCE: While propranolol is touted as superior to prednisolone for treating infantile hemangiomas (IH), a randomized clinical trial (RCT) comparing the outcome and tolerability of these medications for symptomatic, proliferating IH has not been reported. OBJECTIVES: To determine if oral propranolol is more efficacious and better tolerated than prednisolone in treating symptomatic, proliferating IH and to determine the feasibility of conducting a multi-institutional, RCT comparing efficacy and tolerability of both medications. DESIGN, SETTING, AND PARTICIPANTS: Phase 2, investigator-blinded, multi-institutional RCT conducted in 3 academic vascular anomalies clinics on 19 of 44 eligible infants aged between 2 weeks and 6 months. All participating patients had symptomatic proliferating IH treated between September 1, 2010, and August 1, 2012. INTERVENTIONS: Treatment with oral propranolol vs prednisolone (2.0 mg/kg/d) until halted owing to toxic effects or clinical response. MAIN OUTCOMES AND MEASURES: Primary outcome was change in IH size after 4 months of therapy. Secondary outcomes were response rate and frequency and severity of adverse events (AEs). RESULTS: The primary outcome showed no difference in lesion size or affected skin area after 4 months of therapy: 41% and 1.32 mm2 for prednisolone vs 64% and 0.55 mm2 for propranolol (P = .12 for lesion size, and P = .56 for affected skin area). Longitudinal analyses showed a faster response in total lesion outer dimension with prednisolone (P = .03), but this advantage over time was not noted when central clearing and outer dimension were included in the analysis (P = .91). The overall frequency of AEs was similar (44 for prednisolone vs 32 for propranolol) (P = .84), but prednisolone-treated participants had more grade 3 severe AEs (11 vs 1) (P = .01), particularly growth retardation resulting in size and weight below the fifth percentile. Early study withdrawal owing to AEs occurred in 6 (75%) of 8 patients in the prednisolone group but 0 of 11 propranolol-treated participants. The mean duration of therapy was shorter for prednisolone (141 vs 265 days), reflecting the higher rate of early withdrawals. CONCLUSIONS AND RELEVANCE: Both medications show similar efficacy for reducing the area of symptomatic, proliferating IH. Although prednisolone showed a faster response rate, propranolol was better tolerated with significantly fewer severe AEs. Propranolol should be the first line of therapy for symptomatic IH unless contraindicated or unless future studies demonstrate severe AEs from propranolol. Recruiting participants for a phase 3 RCT would be difficult owing to safety profiles measured here and emerging trends favoring propranolol. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00967226.

Cardiovascular and blood glucose parameters in infants during propranolol initiation for treatment of symptomatic infantile hemangiomas.

OBJECTIVES: We sought to determine the effect of propranolol on cardiovascular and blood glucose parameters in infants with symptomatic infantile hemangiomas who were hospitalized for initiation of treatment, and to analyze adverse effects of propranolol throughout the course of inpatient and outpatient treatment. METHODS: A retrospective cohort analysis was performed on 50 infants (age less than 12 months) with symptomatic infantile hemangiomas who were hospitalized for propranolol initiation between 2008 and 2012. Demographic data and disease characteristics were recorded. Systolic and diastolic blood pressures, heart rate, blood glucose values, and adverse events recorded during hospitalization were analyzed. An additional cohort of 200 consecutively treated children was also assessed for adverse events associated with outpatient propranolol use. RESULTS: The median age among the inpatient cohort was 3.4 months (range, 0.8 to 12.0 months). Infants older than 6 months were more likely to exhibit bradycardia than were younger infants (p < 0.001). Hypotensive and/or bradycardic periods were infrequent and were not associated with observable clinical symptoms. The mean systolic and diastolic blood pressures and the mean heart rate decreased significantly from day 1 of hospitalization to day 2 (p = 0.004; p = 0.008; p < 0.001), but not from day 2 to day 3, when the propranolol dose was increased to target. Hypoglycemia was rare (0.3% incidence.) Among the 250 outpatients, 2 infants developed lethargy and hypoglycemia during a viral illness and recovered without sequelae. One infant experienced recurrent bronchospasm with viral illnesses and required concomitant bronchodilator therapy. CONCLUSIONS: Frequent deviations from normal ranges of blood pressure and heart rate occur upon initiation of propranolol, but are clinically asymptomatic. These findings support that outpatient initiation of propranolol in healthy, normotensive infants appears to be a relatively safe alternative to inpatient initiation. Hypoglycemia is rare, but can occur throughout the treatment period; parent counseling is of paramount importance.

Propranolol and infantile hemangiomas four years later: a systematic review.

To systematically review the literature evaluating efficacy and adverse events of propranolol treatment for infantile hemangiomas, we searched the MEDLINE and Cochrane databases for all studies examining the response of infantile hemangiomas (IHs) to propranolol published between June 12, 2008, and June 15, 2012. Forty-one studies with 1,264 patients were included; 74% of patients were female and approximately 30% had received other treatments before propranolol. Propranolol was initiated at a mean age of 6.6 months at a mean dose of 2.1 mg/kg/day and for a mean treatment duration of 6.4 months. The response rate for patients with IHs treated with propranolol was 98% (range 82%-100%), with response rate defined as any improvement with propranolol. Treatment response rates were comparable for studies evaluating IHs at specific sites, such as periorbital IHs. Studies that followed patients after treatment completion reported IH rebound growth in 17% of patients. There were 371 adverse events reported in 1,189 patients. The most common adverse events were changes in sleep (n = 136) and acrocyanosis (n = 61). Serious adverse events were rare, with reports of symptomatic hypotension in five patients, hypoglycemia in four, and symptomatic bradycardia in one. This systematic review of 1,264 patients treated with propranolol for IHs showed a high rate of efficacy and a low rate of serious adverse events.